129S(Cg)-Tfrc^tm3.1Nca/J

Stock number: 028177
Product name: TfR1^fl , Tfrc^fl , Trfr^fl
Research areas: Metabolism Research, Neurobiology Research, Research Tools

Description

Tfr1^fl/fl floxed mice possess loxP sites flanking exons 3-6 of the transferrin receptor gene. This strain may be useful for studying iron uptake.

Detailed description

Tfr1^fl/fl floxed mice possess loxP sites flanking exons 3-6 of the transferrin receptor (Tfrc) gene. Transferrin receptors are transmembrane glycoprotein involved in the cellular uptake of iron via receptor-mediated endocytosis. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 3-6 deleted in cre-expressing tissues.

For example, when crossed to Tg(Vil-cre/ERT2)23Syr mice, expressing Cre recombinase in intestinal epithelium, resulting offspring display severe disruption of the epithelial barrier and early death. They also showed impaired proliferation of intestinal epithelial cell progenitors, aberrant lipid handling, increased mRNA expression of stem cell markers, and induction of many genes associated with epithelial-to-mesenchymal transition.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 3, and a single loxP site downstream of exon 6 of the transferrin receptor (Tfrc) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Resulting chimeric males were bred to Gata1-cre females to delete the neo cassette. Resulting offspring contained multiple gene rearrangments; intact floxed-exons 3-6, intact floxed-neo cassette, or excision of the exons and the neo cassette. Progeny, containing only the floxed-exons, were bred to 129S1/SvImJ mice (Stock No. 002448) and the cre-expressing transgene was bred out of the colony. Subsequently, these mice were bred to 129S6/SvEvTac mice for at least 10 generations. Upon arrival, Tfr1^fl/fl mice were bred to 129S1/SvImJ inbred mice for at least one generation to establish the colony.

Allele

Symbol: Tfrc^tm3.1Nca
Name: targeted mutation 3.1, Nancy C Andrews
MGI accession ID: MGI:5689121
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Tfrc
Marker name: transferrin receptor
Chromosome: 16
Strain of origin: 129S4/SvJae
Molecular note: A loxP-flanked neomycin resistance cassette (neo^r) was introduced into intron 2 and a third loxP site into intron 6. The neo^r was deleted by cre recombinase expression, leaving exons 3-6 flanked by loxP sites.